The pharmacodynamic properties of azithromycin in

Authors: Mark S Dorfman Rudolph S Wagner Tiffany Jamison Belinda Bell David W Stroman

Publish Date: 2008/03/27

Volume: 25, Issue: 3, Pages: 208-217

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Abstract

Antibiotics have traditionally been classified as bactericidal or bacteriostatic Azithromycin belongs to the parent class of macrolides that are characteristically bacteriostatic Some evidence suggests that this molecule demonstrates bactericidal kill and has concentrationdependent effects This study tests the hypothesis that azithromycin demonstrates a bactericidal concentrationdependent antibiotic effect at concentrations corresponding to and exceeding published tear and conjunctival levelsThe antibacterial activity of different concentrations of azithromycin 1 in DuraSite® AzaSite® Inspire Pharmaceuticals Inc Durham NC USA was evaluated using a kineticsofkill model Recent conjunctivitis isolates of Staphylococcus aureus Streptococcus pneumoniae or Haemophilus influenzae were exposed to four concentrations of azithromycin 100 250 500 and 750 μg/ml Starting concentrations were similar to the maximum concentrations Cmax that have been demonstrated in conjunctiva 83 μg/g and tears 288 μg/ml following topical ocular administration The percentage of surviving bacteria at 30 and 60 minutes following exposure to each concentration were determinedAzithromycin failed to demonstrate bactericidal activity ie a 3log reduction in surviving bacteria against S aureus S pneumoniae or H influenzae Furthermore the rate and extent of antibacterial activity with azithromycin did not change with higher concentrations even at the highest tested concentration of 750 μg/mlSimilar to the parent macrolide class azithromycin demonstrates bacteriostatic activity against common conjunctival pathogens up to the maximum tested concentration of 750 μg/ml ie 26times and 9times published Cmax tear and conjunctival concentration respectively Azithromycin’s bacteriostatic effects and prolonged elimination halflife will likely lead to a corresponding increase in the emergence of macrolideresistant isolates

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